CB2 receptors regulate natural killer cells that limit allergic airway inflammation in a murine model of asthma

M. E. Ferrini, S. Hong, A. Stierle, D. Stierle, N. Stella, K. Roberts, Z. Jaffar

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Allergic asthma is a chronic airway inflammatory disease involving the complementary actions of innate and adaptive immune responses. Endogenously generated cannabinoids acting via CB2 receptors play important roles in both homeostatic and inflammatory processes. However, the contribution of CB2-acting eicosanoids to the innate events preceding sensitization to the common house dust mite (HDM) allergen remains to be elucidated. We investigated the role of CB2 activation during allergen-induced pulmonary inflammation and natural killer (NK) cell effector function. Methods: Lung mucosal responses in CB2-deficient (CB2−/−) mice were examined and compared with wild-type (WT) littermates following intranasal exposure to HDM allergen. Results: Mice lacking CB2 receptors exhibited elevated numbers of pulmonary NK cells yet were resistant to the induction of allergic inflammation exemplified by diminished airway eosinophilia, type 2 cytokine production and mucus secretion after allergen inhalation. This phenomenon was corroborated when WT mice were treated with a CB2-specific antagonist that caused a pronounced inhibition of HDM-induced airway inflammation and goblet cell hyperplasia. Unexpectedly, the preponderance of NK cells in the lungs of CB2−/− mice correlated with reduced numbers of group 2 innate lymphoid cells (ILC2s). Depletion of NK cells restored the allergen responsiveness in the lungs and was associated with elevated ILC2 numbers. Conclusions: Collectively, these results reveal that CB2 activation is crucial in regulating pulmonary NK cell function, and suggest that NK cells serve to limit ILC2 activation and subsequent allergic airway inflammation. CB2 inhibition may present an important target to modulate NK cell response during pulmonary inflammation.

Original languageEnglish
Pages (from-to)937-947
Number of pages11
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume72
Issue number6
DOIs
StatePublished - Jun 2017

Keywords

  • CB2 receptors
  • animal models
  • asthma
  • innate immunity
  • natural killer cells

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